Top-down mass spectrometry (TD-MS)-based proteomics analyzes intact proteoforms and thus preserves information about individual protein species. The MS signal of these high-mass analytes is complex and challenges the accurate determination of proteoform masses. Fast and accurate feature deconvolution (i.e., the determination of intact proteoform masses) is, therefore, an essential step for TD data analysis. Here, we present FLASHDeconv, an algorithm achieving higher deconvolution quality, with an execution speed two orders of magnitude faster than existing approaches. FLASHDeconv transforms peak positions (m/z) within spectra into log m/z space. This simple transformation turns the deconvolution problem into a search for constant patterns, thereby greatly accelerating the process. In both simple and complex samples, FLASHDeconv reports more genuine feature masses and substantially fewer artifacts than other existing methods. FLASHDeconv is freely available for download here https//www.openms.org/flashdeconv/. A record of this paper's Transparent Peer Review process is included in the Supplemental Information. Identifying cancer-relevant mutations in noncoding regions is challenging due to the large numbers of such mutations, their low levels of recurrence, and difficulties in interpreting their functional impact. To uncover genes that are dysregulated due to somatic mutations in cis, we build upon the concept of differential allele-specific expression (ASE) and introduce methods to identify genes within an individual's cancer whose ASE differs from what is found in matched normal tissue. When applied to breast cancer tumor samples, our methods detect the known allele-specific effects of copy number variation and nonsense-mediated decay. Further, genes that are found to recurrently exhibit differential ASE across samples are cancer relevant. Genes with cis mutations are enriched for differential ASE, and we find 147 potentially functional noncoding mutations cis to genes that exhibit significant differential ASE. We conclude that differential ASE is a promising means for discovering gene dysregulation due to cis noncoding mutations. The endosomal sorting complex required for transport (ESCRT) machinery carries out the membrane scission reactions that are required for many biological processes throughout cells. How ESCRTs bind and deform cellular membranes and ultimately produce vesicles has been a matter of active research in recent years. In this study, we use fully atomistic molecular dynamics simulations to scrutinize the structural details of a filament composed of Vps32 protomers, a major component of ESCRT-III complexes. The simulations show that both hydrophobic and electrostatic interactions between monomers help maintain the structural stability of the filament, which exhibits an intrinsic bend and twist. Our findings suggest that the accumulation of bending and twisting stresses as the filament elongates on the membrane surface likely contributes to the driving force for membrane invagination. The filament exposes a large cationic surface that senses the negatively charged lipids in the membrane, and the N-terminal amphipathic helix of the monomers not only acts as a membrane anchor but also generates significant positive membrane curvature. Taking all results together, we discuss a plausible mechanism for membrane invagination driven by ESCRT-III. Stroke is one of the leading causes of long-term disability. Advanced technological solutions ("neurotechnologies") exploiting robotic systems and electrodes that stimulate the nervous system can increase the efficacy of stroke rehabilitation. Recent studies on these approaches have shown promising results. However, a paradigm shift in the development of new approaches must be made to significantly improve the clinical outcomes of neurotechnologies compared with those of traditional therapies. An "evolutionary" change can occur only by understanding in great detail the basic mechanisms of natural stroke recovery and technology-assisted neurorehabilitation. In this review, we first describe the results achieved by existing neurotechnologies and highlight their current limitations. In parallel, we summarize the data available on the mechanisms of recovery from electrophysiological, behavioral, and anatomical studies in humans and rodent models. Finally, we propose new approaches for the effective use of neurotechnologies in stroke survivors, as well as in people with other neurological disorders. Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. https://www.selleckchem.com/products/nicotinamide-riboside-chloride.html Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions. In this issue of Neuron, Greene et&nbsp;al. (2020) identify zones of network specificity and multi-network integration in the basal ganglia and thalamus of individual human subjects. Such information could aid in the development of personalized and more effective brain stimulation therapies for neuropsychiatric disorders. Confidence in perceptual decisions scales neural responses to violations in reward expectation. In this issue of Neuron, Lak et&nbsp;al. (2020) show that the medial prefrontal cortex in mice computes a confidence-dependent expectation signal that influences how dopamine neurons convey reward prediction errors to guide learning. In this issue of Neuron, Ashrafi et&nbsp;al. (2020) identify a feedforward signaling mechanism that couples neuronal activity to the homeostatic maintenance of axonal and synaptic ATP production. This mechanism is achieved via changes in cytoplasmic calcium and activation of brain-specific, mitochondrial MICU3. Balance between excitation and inhibition (E-I balance) in neural circuits is believed to be tightly regulated. To the contrary, in this issue of Neuron, Bridi et&nbsp;al. (2020) reveal that inverse oscillations of synaptic inhibition and excitation lead to peaks and valleys in E-I balance across the 24&nbsp;h day. Polymorphism at the 17q21 gene locus and wheezing responses to rhinovirus (RV) early in childhood conspire to increase the risk of developing asthma. However, the mechanisms mediating this gene-environment interaction remain unclear. In this study, we investigated the impact of one of the 17q21 encoded genes, ORMDL3 on RV replication in human epithelial cells. ORMDL3 knockdown inhibited RV-A16 replication in HeLa, BEAS-2B, A549, NCI-H358 epithelial cell lines, and primary nasal and bronchial epithelial cells. Inhibition varied by RV species, as both minor and major group RV-A subtypes, RV-B52 and RV-C2 were inhibited, but not RV-C15 or RV-C41. ORMDL3 siRNA did not affect expression of the major group RV-A receptor ICAM-1 or initial internalization of RV-A16. The two major outcomes of ORMDL3 activity, serine palmitoyl-CoA transferase (SPT) inhibition and endoplasmic reticulum (ER) stress induction were further examined silencing ORMDL3 decreased RV-induced ER stress and IFN-? mRNA expression. However, pharmacologic induction of ER stress and concomitant increased IFN-? inhibited RV-A16 replication.